System for setting programmable parameters for an implantable hypertension treatment device

ABSTRACT

A real time, heart rate monitor and a hemodynamic monitoring system are operably integrated with the programmer system for an implantable hypertension treatment device. A series of tests are automatically performed to set programmable parameters for the implantable hypertension treatment device without clinician intervention. In one embodiment, a predetermined level of a dose-response evaluation is initiated for each test in the series. Preferably, the programmer system monitors the heart rate to determine whether a hemodynamic measurement should be initiated at all for a given test, as well as whether the hemodynamic measurement should be initiated earlier or later than a predetermined settling period for assessing the sympathetic nervous response to the test dose. In one embodiment, this determination is based on heart rate stability/instability. Alternatively, other indicators of sympathetic/parasympathetic tone, such as heart rate variability, may be used to trigger/delay the timing of the hemodynamic measurement.

RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.11/254,042 entitled “System for Setting Programmable Parameters for anImplantable Hypertension Treatment Device” filed Oct. 18, 2005, thedisclosure of which is hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates generally to electrical therapeuticsystems for hypertension treatment. More particularly, the presentinvention relates to methods and apparatus for setting programmableparameters for an implantable hypertension treatment device.

Implantable devices for treating high blood pressure or hypertension bystimulating various nerves and tissue in the body are known anddescribed, for example, in U.S. Pat. No. 3,650,277 (stimulation ofcarotid sinus nerve), U.S. Pat. No. 5,707,400 (stimulation of vagalnerve), and U.S. Pat. No. 6,522,926 (stimulation of baroreceptors).While many aspects of these implantable devices are similar toimplantable devices used to treat cardiac arrhythmias, such aspacemakers and implantable defibrillators, there are significantdifferences in the application and operation of implantable hypertensiondevices due to the fact that the slower responding baroreflex system isbeing stimulated, instead of the rapid response of cardiac stimulationused for pacemakers.

Implantable electronic medical devices typically requirepost-implantation programming of certain parameter values in order toestablish proper patient-specific performance. For example, implantablecardiac stimulation devices, such as pacemakers and implantable cardiacdefibrillators (ICDs) utilize a threshold margin testing procedure inwhich the level of electrotherapy pulses is established for the specificpatient. Each patient will have a unique tissue impedance andsusceptibility to the electrotherapy signaling, and the configuration ofelectrodes can produce different results for the same stimulation pulse.As a result, it is necessary to program certain parameter values in thepacemaker or ICD to establish optimum therapy for that patient for aparticular implantable device and electrode configuration.

In the case of a conventional pacemaker, the object of such parameterprogramming is to establish the voltage level of the pacing pulses suchthat the pulses are of a sufficiently high amplitude to achieve reliablecapture of the patient's heart while being of a minimal amplitude toachieve the desired therapy to provide the longest possible battery lifefor the device. Similarly, in the case of implantable defibrillators,the defibrillation pulse amplitude is set to the minimal level toachieve reliable electrotherapy with minimal tissue damage and maximumbattery life. In each case, the programmable parameters are typicallyset at some safety threshold margin above the measured pacing capture ordefibrillation threshold values.

Automatic systems for testing and configuring the threshold parametersof implantable cardiac stimulation devices are described, for example,in U.S. Pat. Nos. 5,320,643, 5,487,752 and 6,311,089. Examples ofimplantable cardiac stimulation devices that automaticallyself-configure the operating parameters for the device using built-inmeasurement/circuitry and sensors and some type of configurationalgorithm are described in U.S. Pat. Nos. 6,463,325 and 6,587,723. U.S.Pat. No. 6,371,922 describes optimizing cardiac stimulation pulsesdelivered by a pacemaker based on measuring Baroreflex sensitivity.

A common aspect to these conventional automatic device configuringsystems for implantable cardiac stimulation devices is that thephysiological response of the patient is generally readily observable ashort time (on the order of seconds) following an administration ofelectrotherapy by the implantable device. Another common aspect is thatthe physiological response of cardiac stimulation is generally binary innature. Stated another way, the desired physiological response is eitherpresent or absent. In the case of a pacemaker, the pacing pulse for theheart is either captured or not captured; in the case of adefibrillator, the cardiac rhythm is either restored, or not restored.Detecting the presence or absence of these fast and easily discernablephysiological responses to the electrotherapy signals applied to theautonomic nervous system is therefore a relatively straight-forwardendeavor. Furthermore adjustment of the electrotherapy signaling tooptimize device performance in response to the physiological responses(or lack thereof) can be done incrementally in a relatively short periodof time.

By contrast, implantable devices for treating hypertension by regulatingblood pressure in a patient may induce a physiological effect in thesympathetic nervous system that is not binary in nature and that tendsto be protracted or sustained. For example, baroreceptor stimulationeffects an incremental, or gradual, change in blood pressure that isobservable only after a relatively longer period of time (on the orderof minutes). Therefore, conventional automatic device configurationsystems and methods developed for implantable cardiac stimulationdevices are not directly applicable for configuring hypertensiontreatment devices.

Presently, hypertension treatment devices are configured based onmonitoring performed manually by clinical personnel. This process ofdose-response testing for a hypertension treatment devices requires theclinical personnel to have an instrument for taking blood pressuremeasurement of the patient, such as an automated blood pressuremeasurement system like the Dynamap® blood pressure system. In addition,the patient's heart rate must be monitored to insure that the heart ratedoes not drop to a lower than desired value. Therefore, the patient isalso connected to a real time, or continuous, heart rate monitor, suchas a surface ECG or SP0₂ measurement device. Finally, the clinicalpersonnel must manually operate the programmer for the implantablehypertension treatment device to repeatedly perform the testing routinethat typically includes: (a) programming the implantable hypertensiontreatment device, (b) monitoring the heart rate while waiting aprescribed number of minutes to take initiate measurement of thehemodynamic parameters of the patient, (c) manually starting themeasurement of the hemodynamic parameters of the patient, (d) manuallyrecording the results of the hemodynamic parameters of the patient andcorrelating those results to the programmed settings, (e) determining ifthe recorded results indicate whether the dose-response has stabilized,and (f) if not, continue repeating the test process at the next higherdose response level. Presently, all of these instruments are separatefrom the programmer and require separate monitoring and operation fromthe programmer device.

When configuring an implanted hypertension treatment device by this kindof dose-response test process, the clinical personnel must keep track ofissues such as the time until a physiological response to a change inelectrotherapy administration, operation of the device programmer,operation of the blood pressure measuring apparatus, recordingmeasurements, and correlating measurements with the most recentelectrotherapy set point, all while continuously monitoring the safetyof the patient during the procedure by keeping track of the patient'sheart rate. Because such procedures are operator intensive, subject tomeasurement variability, and time-consuming, there are significantdrawbacks to the current methods for configuring implanted bloodpressure regulating devices.

BRIEF SUMMARY OF THE INVENTION

The present invention is a system for automating the setting ofprogrammable parameters for an implantable hypertension treatmentdevice. One aspect of the present invention integrates a real time heartrate monitor and a hemodynamic monitoring system with the programmersystem for an implantable hypertension treatment device. A series oftests are automatically performed to set programmable parameters for theimplantable hypertension treatment device under program control thatpermits automatic operation without clinician intervention. In oneembodiment, a predetermined level of a dose-response evaluation isinitiated for each test in the series. Preferably, the programmer systemmonitors the heart rate to determine whether a hemodynamic measurementshould be initiated at all for a given test, as well as whether thehemodynamic measurement should be initiated earlier or later than apredetermined settling period for assessing the sympathetic nervousresponse to the test dose. In one embodiment, this determination isbased on heart rate stability/instability. Alternatively, otherindicators of sympathetic/parasympathetic tone, such as heart ratevariability, may be used to trigger/delay the timing of the hemodynamicmeasurement.

In one embodiment, the heart rate monitor and hemodynamic measurementsystem are separate devices in communication with the programmer system.In another embodiment, the heart rate monitor and hemodynamicmeasurement system are incorporated into the programmer system. Inanother embodiment, the hemodynamic measurement system and/or the heartrate monitor system may be integrated with the implantable hypertensiontreatment device that is in communication with the programmer. In afurther embodiment, the hemodynamic measurement system and/or the heartrate monitor system may be implanted separately from the implantablehypertension device and could be in communication with the programmer,either directly or via the implantable hypertension device.

The present invention avoids errors that can be associated with theexisting manual testing procedures for setting programmable parametersfor implantable hypertension treatment devices. The present inventionalso permits the testing to be performed more rapidly and with minimalclinician intervention during the procedure. The integration of theprogrammer system in accordance with the present invention improves theoverall safety of the test procedure as the system can more rapidlydetect and respond to a low heart rate condition than manual monitoringand intervention.

Unlike the prior art testing techniques for setting programmableparameters for implantable cardiac stimulation devices, thedose-response characteristics associated with an implantablehypertension treatment device are much more linear in that thehemodynamic response of various programmed conditions needs to bemeasured in order to determine an algorithm or model of the response.The clinician may use the output of this model to guide the clinician inprogramming the parameters of the implantable hypertension treatmentdevice so that the desired hemodynamic response is achieved. The doseresponse procedure of the present invention also takes significantlymore time than, for example, the pacemaker threshold margin test,because the hemodynamic response to certain programmed conditions mayinitiate a response nearly immediately after programming, or it may takeseveral minutes for the patient to achieve a stabilized response.

Preferably, the clinician monitors the test procedure from a remoteviewing/monitoring location. In one embodiment, the programming systemincludes a remote control to facilitate the remote monitoring of thetest procedure. Preferably, the remote control would be connected withthe programming system by a wireless connection, such as RF, infrared oroptical, although it will be recognized that the remote control couldalso be provided with a wired connection. The present inventionrecognizes that even modest amounts of interaction or talking with aclinician can cause a change in the blood pressure of the patient,thereby affecting the results of the test procedure. The automatednature and integration of the present invention permits the clinician toavoid interaction with the patient during the test procedure so as tominimize the chances of inadvertently affecting the results of the testprocedure.

In one embodiment, the hemodynamic measurement system may be adiscontinuous or non-real time measurement system, such as aninflated/deflated cuff where measurements are taken periodically ratherthan continuously. Alternatively, a real-time waveform measurementsystem, such as a Finometer™ blood pressure instrument manufactured byFinapres® or continuous pressure monitor, may be utilized. In theembodiment in which a real-time waveform measurement system is used, thehemodynamic measurement system may be used in place of the heart ratemonitor, or to augment the heart rate monitor, in terms of theassessment of whether a stable response has been achieved for a givendose-response test.

The present invention enables automated and faster integration of datafrom the test results, and in one embodiment graphic display of the testresults, to assist the clinician in determining the desired parametersfor the implantable hypertension treatment device. In this embodiment,the programmer system and/or the implantable hypertension treatmentdevice include data storage for storing dose response characteristics,preferably including historical dose response characteristics for thegiven patient. These dose response characteristics may be displayed tothe clinician for diagnostic purposes, as well as for setting theprogrammable parameters for the implantable hypertension treatmentdevice. In another embodiment, the historical data may also be used toshorten up the test period for the series of dose-response tests. Forexample, if past data has reasonably determined the response thresholdand response slope, a new threshold and slope may be determined with fewtest conditions by, for example, using the previous threshold andresponse slope to interpolate among fewer dose response test points.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overview block diagram illustrating a programming system inaccordance with one aspect of the present invention interfaced with apatient and with a hypertension treatment device implanted in thepatient.

FIG. 2 is a schematic diagram illustrating an exemplary arrangement ofprogramming system components and their interface with one another andwith an hypertension treatment device implanted in a patient.

FIGS. 3A-3D are block diagrams illustrating various examples ofarrangements between a programming system, patient monitors, and animplanted hypertension treatment device within the spirit of theinvention.

FIG. 4 is a schematic diagram illustrating parts of a programmeraccording to one embodiment of the invention.

FIGS. 5A-5B are flow diagrams illustrating various methods ofconfiguring an implanted device via dose-response testing.

FIGS. 6A and 6B are graphs showing the relationship between systolicblood pressure and heart rate as a function of pulse amplitude for aseries of dose-response tests.

FIG. 7 is a flow chart of one method of quickly predicting effectivenessfor each of a plurality of dose-response tests prior to making bloodpressure measurements for a given dose-response test.

FIG. 8 is a is a diagram illustrating one method of skipping/terminatinglevels in a series of dose-response tests based onpredictive/interpolative analysis of previous dose-response test.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 is a schematic diagram illustrating a programmer system 100 for ahypertension treatment device 102 implanted in patient 104. Programmersystem 100 is generally adapted to automatically conduct dose-responsetesting in the patient using the treatment device 102, and to optionallydetermine a suitable operating point or calibration curve for thetreatment device 102 based on the dose-response testing and program theimplanted treatment device 102 accordingly.

Programmer system 100 includes a CPU 106 that is configured withmachine-readable instructions to execute its operating functions. CPU 106 is communicatively coupled with a patient monitoring sub-system 1 08,a device configurator sub-system 110, and operator interface sub-system112. The communicative coupling can include any suitable arrangement forthe exchange of data, control, and other such communication between theaforementioned sub-systems of programmer system 1 00, including a databus, serial communications, analog signaling, wireless communications,and the like, and combinations thereof.

In one type of embodiment, the CPU 106, patient monitoring sub-system108, device configurator sub-system 110, and operator interface 112 areclosely integrated into a single device or system. In other types ofembodiments, one or more of these sub-systems is implemented as aseparate device that is operatively interfaced into the overall system,but not necessarily fully controlled by CPU 106. In one such embodiment,for example, one or more sub-systems have their own CPU (not shown)configured to control only the associated sub-system, and only anexchange of data takes place between loosely-integrated sub-systems(i.e., no control or configuration information is exchanged). Personsskilled in the art will recognize that, for one or more of thesesub-systems, any degree of integration into the greater system is withinthe spirit of the invention.

Patient monitoring subsystem 1 08 reads one or more sensors configuredto observe the physiological condition of patient 104. Preferably,patient monitoring sub-system 108 reads at least the patient'shemodynamic condition. Examples of sensors suitable for taking thesemeasurements include electrocardiogram (EKG) sensors 114, pulse oximetrysensor 116, cuff-type blood pressure sensor 118, and implanted bloodpressure sensor 120. Additionally, hemodynamic monitoring can includecardiovascular resistance information and sympathetic/parasympathetictome information (not shown). Sensors can be discontinuous, ornon-real-time, such as a cuff-type blood pressure measuring device.Sensors can also be of the continuous type, such as a Finometer™ bloodpressure instrument manufactured by Finapres®. As illustrated, theimplanted blood pressure sensor 120 can be a part of implanted treatmentdevice 102. Similarly, the implanted treatment device can include otherhemodynamic sensors, such as a heartbeat sensor (not shown) or bloodoxygenation sensor (not shown). Patient monitoring subsystem 108 isinterfaced with each of the respective sensors via suitable hardware.For example, in one embodiment, patient monitoring subsystem 108 isconnected to the EKG sensors via an EKG system 122. In one embodiment,patient monitoring subsystem 108 receives information based on a sensedcondition by the implanted treatment device 102 via communicationchannel 124. Communication channel 124 can be over any suitablecommunications media, including via conductive material, viaelectromagnetic radiation (heat, light, radio, etc.), via mechanicalsignaling such as ultrasonic transduction, and the like. In oneembodiment, communication channel 124 is common with communicationchannel 126 between implanted device 102 and device configuratorsub-system 110.

Patient monitoring subsystem 108 monitors one or more of these sensors,or other suitable sensors (and supplies electrical power, air pressure,or other appropriate enablement needed to facilitate operation of thesensors), converts each sensor's reading into a form suitable forreading by the CPU, and communicates the sensor information to the CPUaccording to the established communications protocol.

Device configurator sub-system 110 includes hardware and/or software forcommunicating with implanted treatment device 102 over communicationchannel 126. Communications over channel 126 include device configuratorsub-system 110 reading status, data, and other relevant informationoriginating in the treatment device 102, and transmitting configurationinformation, calibration, or instructions to the treatment device 102.Communication channel 126 can be over any suitable communications media,including via conductive material, via electromagnetic radiation (heat,light, radio, etc.), via mechanical signaling such as ultrasonictransduction, and the like.

Operator interface 112 permits a human user of system 100, such as aclinician, to observe the operation of system 100, including monitoringthe patient's sensed condition, the activity of implanted treatmentdevice 102, and the progress of programming the treatment device 102. Inone embodiment, information is displayed to the clinician in a graphicalformat, such as time-based rolling plots of selected patient conditions,together with the progress of the dose-response testing. Such a display,which includes providing stored historic dose-response data of thepatient, can enable the clinician to readily identify any particulartrends in the dose-response test results.

In a preferred type of embodiment, operator interface 112 also enablesthe clinician to manually control the dose-response testing,determination of operating point for implanted device 102, and/or theprogramming of the implanted device 102 to a selectable extent. In oneexample embodiment of this type, an operator has the option of runningthe system 100 in a fully automatic mode, or exercising some level ofcontrol over patient monitoring, dose-response testing, analysis of thedose-response testing results, or configuring of the implanted device102. In one embodiment, operator interface 112 is configured to acceptmanually inputted data representing a condition of the patient forincorporation into the analysis of the dose-response testing.

Operator interface 112 can be integrated closely with one or moresub-systems of system 100 such that CPU 106 controls operator interface112. Alternatively, operator interface 112 can itself be a separatedevice that merely exchanges data with CPU 106. In this latterembodiment, operator interface 112 can be implemented in a personalcomputer (PC) running an application program that enables the PC tointerface with CPU 106 and facilitate the user display and inputs. Inone embodiment, operator interface 112 can be interfaced with CPU 106over a computer network. Preferably, operator interface 112 is situatedremotely from the patient to minimize the undesirable effect on theaccuracy of measurement of the patient's condition resulting frominteraction between the clinician and patient.

FIG. 2 illustrates an exemplary arrangement of components of aprogramming system 200 and their interface with one another and with ahypertension treatment device 202 implanted in a patient 204.Programming system 200 includes a programmer 206, which has processor208 interfaced with communications circuit 210 via interface 209 betweenprocessor 208 and communications circuit 210 can be a PCI bus, I2C bus,or any other suitable interface known in the art. Processor 208 includesat least a CPU core and memory MEM. Communications circuit 210 includestransceiver circuitry coupled with an antenna 212 for communicating withcommunications circuit 214 of implanted hypertension treatment device202.

Programming system 202 further includes heart rate monitor 216 andhemodynamic monitor 218. As illustrated in FIG. 2, these components areinterfaced with processor 208 via bus 222, which can be the sameinterface as interface 209, or another suitable interface known in theart. Heart rate monitor 216 and hemodynamic monitor 218 are eachoperatively interfaced with the patient 204 to measure the patient'sphysiological conditions, as represented by the double-dashed lines andindicated at 204′.

Operator interface 220 is operatively coupled with processor 208 viainterface bus 224. Interface bus 224 can be the same interface asinterface 222, or can be another suitable interface.

Implanted hypertension treatment device 202 includes CPU 226 that isconfigured to control the operation of the device. CPU 226 can detectthe need for applying electrotherapy via patient monitoring circuitrythat includes blood pressure measuring circuit 228 interfaced withimplanted blood pressure sensor 230, and via pulse measuring circuit 232interfaced with implanted pulse sensor 234. CPU 226 is furtherconfigured to administer the electrotherapy via electrotherapy circuit236 and electrodes 238.

Heart rate monitor 216 and hemodynamic monitor 218 are interfaced withthe exterior of the patient. In another type of embodiment, heart ratemonitor 216 and hemodynamic monitor 218 are implanted in the patient andinclude data gathering and communication electronics for acquiring thepatient's physiological conditions and transmitting data representingthe same to CPU 208 via communications circuit 210. In this type ofembodiment, heart rate monitor 216 and hemodynamic monitor 218 caneither operate independently of implanted hypertension treatment device202, or can communicate information to the treatment device 202.

In operation, programming system 200, according to one embodiment, canverify that heart rate monitor 216 and hemodynamic monitor 218 providesubstantially similar indicia of the patient's physiological state asprovided via blood pressure measuring circuit 228 and pulse measuringcircuit 232. If these indicia are dissimilar to an unacceptable degree,programming system 200 can calibrate the measuring circuits 228 and 232of implanted device 202, or the implanted device's interpretation of themeasurement data generated by the measuring circuits 228 and 232.Programming system 200 is further configured to conduct a set ofdose-response tests by commanding implanted device 202 to systematicallyvary the therapy dosage over time, while monitoring the effect of thetherapy on the patient's physiology via at least one of heart ratemonitor 216, hemodynamic monitor 218, blood pressure measuring circuit228, and/or pulse measuring circuit 232. As will be discussed in detailbelow, one aspect of the invention is directed to the use of pulse, orheart rate measurement in lieu of hemodynamic or blood pressuremeasurement to reduce the time needed to conduct each dose-responsetest.

FIGS. 3A-3D illustrate various examples of measurement arrangements formonitoring the patient's physiology during the dose-response testing. InFIG. 3A, implanted hypertension treatment device (IHTD) 300 is situatedon the internal side of patient boundary 302. Programmer 304 iscommunicatively coupled with IHTD 300. Heart rate monitor (HRM) 306 andhemodynamic monitoring system (HMS) 308 are operably coupled toprogrammer 304 and, during system operation, are physically engaged withthe patient's exterior. In one embodiment, one or both of HRM 306 andHMS 308 are integrated with the programmer 304. In another embodiment,at least one of HRM 306 and HMS 308 are separate devices electricallyinterconnected with programmer 304.

In FIG. 3B, heart rate monitor HRM 310 and hemodynamic monitoring system312 are implanted in the patient as part of IHTD 300. Programmer 304receives patient physiology information from one or both of HRM 310and/or HMS 312, which information is collected and analyzed during thedose-response testing. In this embodiment, additional external heartrate monitoring or hemodynamic monitoring is avoided.

By contrast, the example arrangement of FIG. 3C has external heart ratemonitoring and hemodynamic monitoring facilitated respectively by HRM306 and HMS 308. This arrangement is similar to the arrangementdescribed above with reference to FIG. 2. One advantage of havingavailable externally-measured physiology information in addition to 30internally-measured physiology information by the IHTD is theexternally-measured condition of the patient can be used by theprogrammer 304 verify accuracy of the internally-measured condition. Inone embodiment, programmer 304 calibrates the measurements of internalHRM 310 and HMS 312.

In another embodiment, programmer 304 configures IHTD 300 to supplytherapy dosage based on the internally-measured physiology data by HRM310 and HMS 312 irrespective of whether these measurements are accuraterelative to the externally-measured physiologic condition of the patientby external HRM 306 and HMS 308. The calibration of IHTD 300 achievedthrough the dose response testing carried out by programmer 304correlates the physiology information obtained from internalmeasurements with those obtained from the external measurements.Assuming, for example, that the external measurements obtained by HRM306 and HMS 308 are an accurate representation of the patient's actualcondition, programmer 304 will establish the appropriate therapy dosagebased on the externally-obtained physiology information. Aftercalibration, the IHTD 300 will administer the established therapy dosageaccording to physiologic measurements made by internal monitors HRM 310and HMS 312, which represent the patient's actual condition 15 to IHTD300.

The example arrangement illustrated in FIG. 3D is similar to thearrangement of FIG. 3C in that programmer 304 gathers patient physiologydata from HRM 306 and HMS 308 that are separate from HRM 310 and HMS 312integral to IHTD 300. However, in the arrangement of FIG. 3D, HRM 306and HMS 308 are implanted in the patient and communicatively coupled toprogrammer 304 through patient boundary 302.

Persons skilled in the relevant arts will appreciate that variations andcombinations of the example embodiments of FIGS. 3A-3D are all withinthe spirit of the invention. Thus, referring to FIGS. 3C and 3D forexample, HRM 306 can be implanted in the patient as depicted in FIG. 3D,while HMS 308 can be external to the patient, as depicted in FIG. 3C. 25Persons skilled in the art will also appreciate that the requisitephysiologic information for assessing the patient's actual condition canbe obtained with only a hemodynamic monitoring system such as HMS 308,i.e., without heart rate monitoring. Thus, the arrangements in FIGS.3A-3D and their variants and combinations having only HMS 308, HMS 312,or both, (without HRM 306 and/or HRM 310) are all within the spirit ofthe invention. Alternatively, as described below, certain embodiments ofthe invention can benefit from heart rate monitoring in addition to, andsometimes in lieu of, hemodynamic monitoring alone.

FIG. 4 is a schematic diagram illustrating one embodiment of aprogrammer 400 for configuring an implanted hypertension treatmentdevice. Programmer 400 can be used with patient monitoring devices orhardware to establish a programming system such as system 100 (FIG. 1)or system 200 (FIG. 2). Programmer 400 can also be used as an embodimentof programmer 304 (FIGS. 3A-3D). Components of programmer 400 include aCPU 402, which includes a processor core such as digital signalprocessor (DSP) 408, instruction memory space 404, and data storagespace 406. In operation, programmer 400 is interfaced with patientmonitoring and other equipment via interface multiplexer (MUX) 410. MUX410 selectively supplies patient monitoring signaling toanalog-to-digital converter (AID) 412, which feeds CPU-readable data toCPU 402. MUX 410 can be digitally controlled directly from CPU 402.

Programmer 400 also includes a wireless communications transceiver 414for facilitating communications with the implanted device. An internalcommunications bus 418 facilitates data exchange between CPU 402 and theother components of programmer 400. Communications bus 418 can have anysuitable bus architecture, as known by persons skilled in the art,including, but not limited to, PCI, SCSI, CAN, I²C, USB, and the like.

As depicted in FIG. 4, programmer 400 is interfaced with a userinterface 416. Preferably, user interface 416 is remote from programmer400. Positioning a clinician operating programmer 400 remotely from thepatient during the dose-response testing can realize an advantage byeliminating inadvertent conversations between the clinician and thepatient, which are known to adversely impact the accuracy of hemodynamicmeasurements. To this end, in a preferred embodiment, user interface 416is communicatively coupled with CPU 402 via interface 420 that issuitable for communications over a relatively larger distance thaninterface 418. In one such embodiment, interface 420 is an Ethernet or awireless IEEE 802.11G Wi-Fi-type interface that facilitates operatorcontrol of programmer 400 from a remote location, such as a differentroom. In one embodiment, interface 420 is operatively coupled with bus418 via network interface controller (NIC) 422.

One aspect of the invention is directed to a method of automaticallyconfiguring, or programming, an implanted hypertension treatment device.In one embodiment, the method can be performed without clinicianintervention. Optionally, a clinician can monitor the progress of thedevice configuring process, and intervene if appropriate. One motivationfor conducting such programming or configuring is to discover theoptimal settings for the implanted hypertension treatment device. In anembodiment in which the implanted device utilizes electrotherapy toregulate blood pressure in the patient, for example, it is desirable forthe device to consume a minimal amount of electrical energy to preservebattery life, while ensuring an effective and reliable degree oftherapeutic effectiveness, or performance, with a safety margin.According to one type of configuration algorithm, the dose-responsetesting is conducted such that the therapy dosage administered by theimplanted device is incrementally varied according to a predefinedsequence, while the effect of the therapy is monitored. The programmingsystem analyzes the results of the tests, and determines the propersettings for various adjustable parameters of the implanted device.

FIG. 5A illustrates a routine 500 according to one embodiment of theinvention for conducting dose-response testing to establish desiredsettings or configuration of an implanted hypertension treatment device.A programming system, such as system 100 (FIG. 1) or system 200 (FIG. 2)is configured to begin the routine according to a default set of routineparameters, such as initial dosage level, step changes in dosage level,settling time, hemodynamic measurement duration, and hypertensiontreatment effectiveness assessment criteria. At 501, the programmingsystem measures the patient's baseline hemodynamic condition (i.e.,without the administration of therapy by the implanted device). At 502,the system issues a command to the implanted device that instructs thedevice to administer the first level of therapy. Because the physiologicresponse of the patient to hypertension therapy may not be immediate, at504, the system waits for a settling period until the beginning of themeasurement window. During this settling period, the hemodynamicmeasurement in the patient should approach a steady state. Depending onthe patient, administered therapy dosage level, type of therapy, type ofphysiologic monitoring, and other such factors, the settling period canrage from several seconds to 5 minutes or more before a reliablemeasurement can be made for assessing the effectiveness of theadministered dosage.

At 506, the system measures the patient's hemodynamic condition over amonitoring time duration. The monitoring time duration can also rangefrom several seconds to 5 minutes or more. In one configuration, thetotal time between administration of therapy is as little as 15 seconds.In another configuration, the total time is at least a minute. Personsskilled in the art will appreciate that this time can be suitablyconfigured as required to obtain accurate and reliable measurements ofthe patient's status. Whichever settings are configured for the settlingtime or measurement period, the automated system is able to consistentlyand accurately follow the timing protocol for each dose-response test,thereby achieving an improved repeatability over manually-performedmeasurements. Measurement of the hemodynamic condition includes, but isnot limited to, measurement of the patient's pulse rate, systolicpressure, diastolic pressure, mean arterial pressure, pulse pressure,blood oxygenation, electrocardiogram information, cardiovascularresistance, sympathetic/parasympathetic tone, and the like.

At 508, the programming system analyzes the effectiveness of the therapybased on the pre- and post-therapy hemodynamic condition measurementsmade. The analysis can be further based on a comparison between actualresults and expected results. In one embodiment, the programming systemwill notify the clinician whenever a greater-than-anticipated differencebetween the actual and expected results is detected. At 510, the systemdetermines whether to continue the dose-response testing. If testing isto continue, the system computes or selects the next therapy dosage forthe implanted device to apply, and the process is repeated beginning at502. Otherwise, if the testing is complete, the system finalizes theprogramming of the implanted device, and exits from the routine.

The programming routine illustrated by the flow diagram of FIG. 5B is avariation of method 500 in which the settling time delay and/or themeasuring window can be automatically and dynamically adjusted. Afterinstructing the implanted device to administer a selected therapy doseat 522, the programming system begins the monitoring the patient'shemodynamic condition relatively soon (e.g. within several seconds), asindicated at 524. During the monitoring, at 526, the programming systembegins building a database of patient condition measurements over time,with dosage and timestamp information included in the records.

Based on the information gathered and analyzed, the system can alsodynamically adjust the default measuring duration and settling timewhile executing a programming routine, as indicated at 528. For example,in a programming system that utilizes both real time (i.e., continuous)and non-real time (i.e., discontinuous) hemodynamic measurementsaccording to one embodiment, the real time measuring begins at 524immediately after therapy administered. Analyzed real time hemodynamicdata as a function of time can indicate an appropriate moment for makinga non-real time measurement. Thus, the physiologic settling time delayfor the non-real time measurement can be automatically varied for eachdose-response test to coincide with the actual time when the patient'scondition has stabilized. Persons skilled in the art will recognize thatthe default measuring duration can be dynamically adjusted in systemswhere only real time measurement is employed.

As part of the measurement data analysis at 528, the programming systemevaluates the shape of the time-based curve generated. This type ofanalysis permits estimation and/or extrapolation of data, and in oneembodiment, is used by the system to shorten the measurement window. Forexample, if the time rate of change of the patient's monitored bloodpressure is not as steep as required for an effective therapy dosage,the system can conclude that a greater dose is needed, and bypass theremaining measurement window, thereby expediting the overall routine.The data collection can also include measurements made over multipledose-response tests. Thus, data curves can be generated and evaluated toanalyze the patient's physiological responsiveness as a function oftherapy dosage.

At 530, the system obtains any additional hemodynamic measurementsneeded to compute the assessment of the effectiveness of theadministered therapy. Based on the assessment, at 532, the systemdetermines whether or not to continue the dose-response testing, andwhich settings to apply to the implanted device in the next loop iftesting is to continue.

FIGS. 6A and 6B are graphs illustrating an exemplary dose-response in apatient. The curve in FIG. 6A represents measurements of the patient'sstabilized systolic blood pressure, while the curve in FIG. 6Brepresents the measured heart rate of the patient. Both curves arefunctions of the dosage applied by an electrotherapy device. The graphsof FIGS. 6A and 6B suggests a significant correlation between the heartrate and blood pressure. Based on this physiologic phenomenon, the heartrate measurement, obtainable over a relatively shorter measurementwindow than the blood pressure measurement, can be used to approximateor predict the patient's blood pressure.

Taking advantage of the correlation between the heart rate and bloodpressure, a method 700 of configuring an implanted device according toone embodiment is illustrated in FIG. 7. At 702, the programming systeminitiates the dose-response testing and configuring loop by initiatinghypertension therapy administration by the implanted device. At 704,soon after the therapy has been administered, the system continuouslymonitors the patient's heart rate. In one embodiment, the system isconfigured to automatically test whether the heart rate is within a saferange. If it is outside the safe range, the clinician is notified andthe dose-response testing is suspended or terminated eitherautomatically or by the clinician. Related embodiments include measuringor determining one or more other factors representing heartbeatinformation including, but not limited to, heart rate stability orinstability, sympathetic or parasympathetic tone, heart ratevariability, and the like.

In another related embodiment, the system processes the heart rate curveas a function of time to predict the time needed for settling of thehemodynamic condition to be measured discontinuously in non-real time.Similarly, one embodiment analyzes the heart rate curve to establish themeasuring window for other hemodynamic measurements to follow.

At 706, the programming system processes at least a portion of thecollected heart rate information to determine if the administered dosagecaused a significant effect on the heart rate. The heart rate analysiscan be performed relatively quickly (i.e. on the order of severalseconds). If the effect is marginal, the system concludes that thedosage is either too small to have any effect on the patient, or thatthe most recently administered dosage is not significantly differentfrom the preceding dosage, and returns to 702 to repeat the loop with adifferent dosage designed to elicit the targeted effect on the patient.In this manner, the system avoids spending time on further hemodynamicmonitoring (which could take more than one minute to complete) andanalysis of a patient condition that is unlikely to be desirable. If, onthe other hand, the effect on the heart rate is measured to besignificant, the system will commit to further hemodynamic conditionmeasurement, analysis, and device configuring as indicated at steps 708,710, and 712.

FIG. 8 is a diagram illustrating a method of configuring an implantedelectrotherapy-type hypertension treatment device that takes advantageof the correlation between heart rate information and blood pressure,and utilizes interpolative and predictive analysis techniques. In FIG.8, the vertical axis generally represents the patient's physiologicconditions including heart rate HR and systolic blood pressure BP. Thehorizontal axis represents the electrotherapy dosage. The Target Rangeis the desired operating point of the implanted device (i.e. the dosageat which the patient's blood pressure is controlled to be within adesirable range). In one embodiment, the programming system firstconducts a series of relatively short-duration dose-response tests,measuring only the patient's heart rate. Reference numerals A-I indicatethe result set of the heart rate dose-response measurements atcorresponding dosages.

The programming system analyzes data set A-I to assess the general shapeof the curve produced as a function of dosage level. Based on certainfeatures of the curve, the programming system determines at which dosagelevels to conduct a series of complete hemodynamic measurements. Forexample, in one embodiment, as illustrated, the first hemodynamicmeasurement α is conducted at the dosage corresponding to heart ratemeasurement A. This initial measurement establishes a baseline, relativeto which subsequent hemodynamic measurements are planned. The secondhemodynamic measurement β is conducted at the dosage corresponding toheart rate measurement F. Heart rate measurement F has been selectedaccording to this exemplary method because it lies at a corner pointwhere the curve slope is approximately −0.5. However, any other suitablecriteria for selecting preliminary and subsequent dosage levels iswithin the spirit of the invention. Because hemodynamic measurement βfalls significantly outside and above the Target Range, the programmingsystem selects the dosage corresponding to heart rate measurement H asthe third hemodynamic measurement point, producing hemodynamicmeasurement γ. Measurement γ is only marginally within the Target Range,so the programming system next conducts a hemodynamic measurement at thenext lowest dosage corresponding to heart rate measurement G, resultingin hemodynamic measurement δ, which is marginally outside of the TargetRange.

Next, the system proceeds to interpolate between the last twohemodynamic measurements δ and γ, favoring a dosage closer to the dosagecorresponding to hemodynamic measurement γ because it is closer to thecenter of the Target Range. The result of the interpolation ishemodynamic measurement ε, which is substantially near the center of theTarget Range. The dosage level corresponding to hemodynamic measurementε is the level for which the system will configure the implantedelectrotherapy device. This example method of arriving at the finaldosage required only five hemodynamic measurements, compared with eightor nine measurements that would have been made if the programmingroutine had utilized a simpler incremental approach.

For a more detailed description of one embodiment of a user interfaceadaptable for use with the present invention, reference is made to “UserInterface for Programming/Monitoring Non-Cardiac Tissue StimulatorDevices,” Ser. No. ______, filed ______, the disclosure of which ishereby incorporated by reference. For a background reference ofimplantable devices for treating high blood pressure or hypertension bystimulating various nerves and tissue in the body, reference is made toU.S. Pat. No. 3,650,277 (stimulation of carotid sinus nerve), U.S. Pat.No. 5,707,400 (stimulation of vagal nerve), and U.S. Pat. No. 6,522,926(stimulation of baroreceptors), the disclosure of each of which ishereby incorporated by reference.

Various modifications to the method may be apparent to one of skill inthe art upon reading this disclosure. The above is not contemplated tolimit the scope of the present invention, which is limited only by theclaims below.

1-20. (canceled)
 21. A system for setting programmable parameters for animplantable baroreflex stimulation device, comprising: an implantablebaroreflex stimulation device including an electrode configured to beimplanted on or in a blood vessel proximate one or more baroreceptors ina wall of the blood vessel; and a programming system communicativelyinterfaced with the implantable baroreflex stimulation device and with ahemodynamic monitoring system configured to collect informationrepresenting a hemodynamic response of the patient over a monitoringtime duration, the programming system being configured to: cause theimplantable baroreflex stimulation device to initiate an electrotherapydose-response test, the test including: delivering a plurality ofelectrotherapy doses of varying levels to the one or more baroreceptorsof the patient via the electrode; and for each electrotherapy dose,selectively processing the information representing the hemodynamicresponse of the patient for the monitoring time duration for thatelectrotherapy dose to establish a patient-specific electrotherapy doseresponse relationship between the electrotherapy dose and thehemodynamic response of the patient; program the implantable baroreflexstimulation device with at least one operating parameter based at leastin part on the patient-specific electrotherapy dose-responserelationship subsequent to establishing the patient-specificelectrotherapy dose-response relationship.
 22. The system of claim 21,wherein the programming system is operatively interfaced with a heartrate monitoring system and the programming system is adapted to monitorinformation representing a heart rate of the patient from the heart ratemonitoring system and provide an alert if the heart rate is outside ofan expected range.
 23. The system of claim 22, wherein the programmingsystem further processes information representing the heart rate of thepatient to evaluate effectiveness of the dose-response test.
 24. Thesystem of claim 21, wherein the information representing a hemodynamicresponse includes at least one hemodynamic information type selectedfrom the set consisting of: pulse rate information; systolic pressureinformation; diastolic pressure information; mean arterial pressureinformation; pulse pressure information; oxygenation information;electrocardiogram information; cardiovascular resistance; andsympathetic/parasympathetic tone information.
 25. The system of claim21, wherein the programming system is further configured to set the atleast one operating parameter of the implantable baroreflex stimulationdevice based at least in part on the patient-specific electrotherapydose-response relationship to achieve a desired performance goal basedupon consuming a minimal amount of energy of the implantable baroreflexstimulation device while achieving a desired effect in the patient. 26.The system of claim 21, wherein the programming system is configured tointerface with a hemodynamic monitoring system according to anarrangement selected from the set consisting of: a separate device incommunication with the programmer system, a system incorporated into theprogrammer system, and a system integrated with the implantablebaroreflex stimulation device.
 27. The system of claim 21, wherein theprogramming system further comprises an operator interface that enablesa clinician to observe and adjust operation of the system and to provideinput utilized to at least alter how the at least one operatingparameter is set.
 28. The system of claim 27, further comprising datastorage memory in operable communication with at least one of theprogrammer system and the implantable baroreflex stimulation device, thedata storage memory configured to store historical data representing theelectrotherapy dose-response relationship.
 29. The system of claim 21,wherein the programming system is configured to automatically performthe plurality of dose-response tests.
 30. The system of claim 22,wherein the programming system is further adapted to selectively processthe information representing the heart rate to evaluate effectiveness ofthe dose-response test.
 31. A method of establishing programmableparameters for an implantable baroreflex stimulation device in a patientcomprising: providing a programming system that is configured to performthe steps of: causing the implantable baroreflex stimulation device toinitiate an electrotherapy dose-response test, the test including:delivering a plurality of electrotherapy doses of varying levels to oneor more baroreceptors of the patient via an electrode implanted on or ina blood vessel proximate the one or more baroreceptors in a wall of theblood vessel; monitoring information representing a hemodynamic responseof the patient over a monitoring time duration for each of the pluralityof electrotherapy doses; and establishing a patient-specificelectrotherapy dose response relationship between the electrotherapydose and the hemodynamic response; using the programming system toprogram the implantable baroreflex stimulation device with at least oneoperating parameter based at least in part on the patient-specificelectrotherapy dose-response relationship subsequent to establishing thepatient-specific electrotherapy dose-response relationship.
 32. Themethod of claim 31, further comprising: monitoring informationrepresenting at least a heart rate of the patient over a testing timeduration of at least several minutes and providing an alert if the heartrate is outside an expected range.
 33. The method of claim 32, whereinthe programming system is configured to perform the further step ofevaluating the information representing at least the heart rate todetermine whether to adjust the monitoring time duration to be greaterthan or less than a predetermined settling period for assessing asympathetic nervous response to the electrotherapy dose.
 34. The methodof claim 33, wherein the step of evaluating the information representingat least the heart rate to determine whether to adjust the monitoringtime duration evaluates at least one of a set of factors in theinformation representing at least the heart rate consisting of: heartrate stability, heart rate instability, sympathetic/parasympathetictone, and heart rate variability.
 35. The method of claim 31, whereinthe step of using the programming system to set a programmable operatingparameter is accomplished by the programming system based on adetermination of the effectiveness of the dose-response test to achievea desired performance goal based upon consuming a minimal amount ofenergy by the implantable baroreflex stimulation device while achievinga desired degree of therapy plus a safety margin.
 36. The method ofclaim 31, wherein the programming system further comprises an operatorinterface and wherein the step of using the programmable system to setthe at least one operating parameter uses the operator interface topermit a clinician to provide input utilized at least to alter how theat least one operating parameter is set.
 37. The method of claim 31,further comprising maintaining a record of previously monitoredhemodynamic responses and wherein the step of using the programmingsystem to set a programmable operating parameter of the implantablebaroreflex stimulation device is based on the record.
 38. The method ofclaim 31, wherein the information representing a hemodynamic responseincludes at least one hemodynamic information type selected from the setconsisting of: pulse rate information; systolic pressure information;diastolic pressure information; mean arterial pressure information;pulse pressure information; oxygenation information; electrocardiograminformation; cardiovascular resistance; and sympathetic/parasympathetictone information.
 39. A method, comprising: providing an implantablebaroreflex stimulation device to a user, the implantable baroreflexstimulation device including an electrode configured to be implanted onor in a blood vessel proximate one or more baroreceptors in a wall ofthe blood vessel; providing a programming system to a user, theprogramming system communicatively interfaced with the implantablebaroreflex stimulation device and with a hemodynamic monitoring systemconfigured to collect information representing a hemodynamic response ofthe patient over a monitoring time duration; and providing instructionsrecorded on a tangible medium to the user, the instructions for settingprogrammable parameters for the implantable baroreflex stimulationdevice, the instructions comprising: initiating an electrotherapydose-response test, the test including: delivering a plurality ofelectrotherapy doses of varying levels to the one or more baroreceptorsof the patient via the electrode; and selectively processing theinformation representing the hemodynamic response of the patient for themonitoring time duration for each electrotherapy dose; establishing apatient-specific electrotherapy dose response relationship between theelectrotherapy dose and the hemodynamic response of the patient; andprogram the implantable baroreflex stimulation device with at least oneoperating parameter based at least in part on the patient-specificelectrotherapy dose-response relationship subsequent to establishing thepatient-specific electrotherapy dose-response relationship.
 40. Themethod of claim 39, wherein providing an implantable baroreflexstimulation device to a user comprises causing an implantable baroreflexstimulation device to be manufactured and made available to a user, andfurther wherein providing a programming system to a user comprisescausing a programming system to be manufactured and made available to auser.